The problem with the current chimpanzee model for evaluating HIV prophylactics is both availability and cost of the animals. Similarly, the SIV model is limited since protection studies in primates illustrated that the immune protective epitopes of SIV envelope glycoprotein are structurally very different from its HIV counterpart. SHIV-LAI is a hybrid SIV virus in which the tat, rev, and env genes have been replaced by their HIV-LAI counterparts. The hybrid virus replicates efficiently in macaques cynomolgus and induces viral specific immune responses. To develop this model for the evaluation of HIV prophylactics, a large scale preparation of SHIV-LAI will be generated to characterize the infection of both cynomolgus and rhesus macaques, and to determine the AID50 using various routes of infection. Additional SHIV viruses will be prepared from HIV-MN, HIV-ADA, HIVYU2, HIVELI, and HIV-Chiang Mei in order to evaluate the cross strain protection afforded by vaccine candidates.